The tal-1 gene is altered as a consequence of the t(1;14)(p34;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). An additional 25% of T-ALL patients bear rearrangements of the tal-1 gene that arise as a consequence of local DNA deletions. Therefore, structural alteration of the tal-1 gene, either by t(1;14)(p34;q11) translocation or local DNA deletion, represents the most common genetic lesion associated with human T-ALL. The tal-1 gene encodes a helix-loop-helix (HLH) domain, a DNA-binding motif found in a number of proteins involved in the control of cell growth and differentiation. The HLH domain of tal-1 is especially related to that of lyl-1, a gene on chromosome 19 that was also identified on the basis of chromosomal rearrangement in human T-ALL. Hence, lyl-1 and tal-1 constitute a family of related HLH proteins implicated in the development of T-ALL. We have recently identified a sequence (designated tal-2) that potentially represents a third member of the lyl/tal family and, as such, may also be involved in T-ALL formation. The general aims of this project are to evaluate the normal functions of the tal-2 gene and to determine whether alteration of this gene promotes the development of T-ALL. The specific aims are to determine the structure of the tal-2 gene and its transcription products; to determine the chromosomal location of the tal-2 gene; to investigate whether tal-2 suffers structural alterations in T-ALL cells; to compare the expression pattern of tal-2 during normal and malignant T cell development; and to examine potential interactions between tal-2 and other HLH proteins implicated in lymphoid leukemia.